Lecture Exam 4

animal viral replication

* Share the same 5 stages as lytic bacteria
* There are some changes because many animal viruses are enveloped
* There are some differences between DNA and RNA viruses

Attachment

* Animal viruses do not have tail fibers. Instead they use glycoprotein spikes to attach to host cells

Entry and Uncoating

* There are three methods for viruses to enter animal cells
* Direct Penetration – done by some naked viruses
* Has correct type of spike proteins to bind with receptors
* Can inject genome into the cell
* Membrane fusion – phospholipid of the viral envelope fused with host cell
* Because they are enveloped, they can bind onto the cell 
* Endocytosis – when the virus trigger receptors on the cell surface to engulf the entire virion
* Triggers macrophages to eat it because it is not recognized by the cell
* Virus infects the cell that engulfs it
* Happens with HIV (macrophages, helper cells, lymphocytes)

bacteriophage vs animal virus

Bacteriophages inject DNA into the host cell, whereas animal viruses enter by endocytosis or membrane fusion

dsDNA synthesis

* Similar to replication of normal cellular DNA and translation or proteins
* Replication usually happens in the nucleus

ssDNA synthesis

* Animal cells do not use ssDNA


* When a ssDNA virus enters a cell, the host will synthesize a complementary strand of DNA to viral genome 
* Then replication and protein synthesis will proceed 

\+ssRNA 

* Ribosomes of the host cell directly translate proteins using the codons of these types of viruses 


* Codes for proteins allowing the viruses to remake its capsid 
* Essentially the +ssRNA viruses as a mRNA recognized by the cell 
* Makes a complimentary strand of –ssRNA 
* Then if it keeps making copies of negative sense of RNA then it can continue to propagate 


* poliovirus is a common example

\+ssRNA (retrovirus) synthesis

* Do not use their genome as mRNA 
* Instead they use reverse transcriptase to create a new strand of cDNA the cell will then use 
* The newly made DNA serves as a template to make more of the retrovirus and as the template for genome of the virus 
* HIV is the most well-known retrovirus

\-ssRNA synthesis

* Host ribosomes cannot translate a -RNA strand 
* A positive sense strand looks exactly like mRNA 
* Negative sense are just opposite direction 


* These viruses carry RNA dependent RNA transcriptase in their capsids 


* The enzyme then creates +RNA strands which can serve as mRNA for creating more of the virus’ genomes as well as proteins 
*  A very common disease is influenza 

dsRNA synthesis

* the +RNA strand can act directly as mRNA 
* The -RNA strand can be transcribed into +RNA and then translated 


* Certain rotaviruses have this type of genome which causes gastroenteritis 

lysis

the breakdown of a cell caused by damage to its plasma (outer) membrane

budding

many enveloped viruses incorporate phospholipid membranes from their host cells as they are released

phage lysogeny

can cause the phenotype of the bacterium to change from harmless into pathogenic

how cells can become cancerous

* Viruses are thought to cause some 20-25% of human cancers


* The most well-known is cervical cancer caused by HPV (Human Papilloma Virus)
* Protooncogenes – are genes in a host cell involved in normal cell division.

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Two Hit hypothesis

* a virus inserts a promotor that converts a protooncogene into an oncogene
* Often this first hit doesn’t cause cancer, but if a second hit damages the downstream repressor gene, \n then the oncogene disrupts cell division and causes cancer

ethical and practical difficulties to overcome in culturing viruses

* Using live organisms create ethical difficulties
* Cell cultures are costly

plaque assay

* Look to see if virus eats through it 
* To estimate phage numbers, you assume that each plaque corresponds to a single phage in the original bacterium/virus mixture

prion diseases

* Bovine Spongiform Encephalopathy (BSE) 


* Chronic Wasting Disease (CWD) 
* in deer and elk
* vCJD – variant Creutzfeldt Jacob Syndrome
* in humans 
* Scrapie 
* Kuru 

prions

Proteinaceous infectious particles

* In human prion diseases a normal PrP protein’s structure becomes altered and begins to affect other \n PrP proteins around it
* As more of the altered PrP proteins aggregate it causes neurons to die and leave holes in the brain
* Diseases caused by prions are called spongiform encephalopathies
* Ingestion of injected tissue, transplants of infected tissue or contact between infected tissues and \n mucous membranes can transmit prion diseases

control and get rid of prions

* in animals they kill the entire herd
* They are not removed through normal autoclaving or decontamination processes
* Sustained heat for several hours at extremely high temperatures (900°F and above) will reliably destroy a prion

4 types of symbiosis

1. mutualism
2. commensalism
3. amensalism
4. parasitism

commensalism

* The microbe benefits without affecting the host – many types of gut bacteria
* These may be mutual and we just haven’t figured it out yet

mutualism

* Both host and microbe benefit from the interaction
* The relationship is beneficial to both, but not necessary

amensalism

* When one symbiont is harmed a second symbiont, while the second is neither harmed or helped by the first
* E.g. – Pencillum fungus makes the antibiotic penicillin which inhibits nearby bacteria, but the bacteria have no effect on the fungus

parasitism

* The parasite gets benefit from the host while causing it harm or disease
* Any parasite that causes disease is called a pathogen
* Which type of parasites would be most effective?
* ones that keep host alive

microbiome

Human microbiome/normal flora/microbiota

* Strep is a large member of the upper respiratory tract
* Most of the fungal members are candida
* Candida albicans has colonized pretty much everyone
* Doesn’t really cause any issues unless the pH changes or immunocompromised

upper digestive tract microbiome

Oral cavity

* Streptococcus
* Lactobacillus
* Probiotic yogurts
* Treponema
* Spirochetes
* Palladium – syphilis

lower digestive tract microbiome

Small intestine

* Lactobacillus
* Enterococcus

Large intestine

* Dense and diverse microbial population
* Klebsiella
* Enterococcus
* Fecal coliforms

female reproductive tract microbiome

Primarily vaginal canal 

* Lactobacillus 
* Staphylococcus 


* Streptococcus 
* Candida  

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Babies born vaginally are colonized with other microorganisms that those delivered by caesaria

skin microbiome

Primarily populated with gram positive organisms 

* Staphylococcus 
* Streptococcus 
* Corynebacterium 
* Propionibacterium 

resident microbiota

Most are commensals 

transient microbiota

* Things we pick up from environment around us and other people 
* Found in same places as resident bacteria 
* Until dislodged by competition 
* Discovered by immune system 
* If causing disease immune system will pick it up 


* Best way to get rid of them is washing hands 

acquisition of microbiome

* Begins at birth 
* Axenic environment – completely free of bacteria 
* Moms' womb 


* Initially colonized when we pass through the birth canal 


* Breastfeeding introduces bacteria that will become gut bacteria

conditions that cause normal flora to be pathogenic

1. introduction of normal microbiota into an unusual site in the body


1. E coli introduced from the digestive tract into the urethra can cause UTIs
2. Immune Suppression


1. Anything that suppresses the normal immune response of our body
2. Post surgery/injury
3. Steroids work to hurt the injury cascade 
* Why c. diff. Is common
3. Changes in the normal microbiome


1. Normal microbiota provide a competitive environment for incoming pathogens
2. antibiotics can allow transients to get a foothold
4. Stressful conditions


1. Emotional or Physicals stressors can allow pathogens to have a competitive advantage
2. Can allow pathogens to get a competitive advantage 
* Cold sores, candida 

3 types of reservoirs

Animals 

* Zoonoses 


* Hard to eradicate because there are so many ways in which we interact with animals (food,

waste processing, pets, etc.)

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Human Carriers 

* Can be asymptomatic for years 
* Typhoid Mary 

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Nonliving Reservoirs 

* Soil, water, food 

contamination

* The presence of microbes in the body 


* Can have no effect 
* They can become part of our normal flora. 
* Remain as transients for a time 
* Become pathogens 

infection

* When the pathogen overwhelms the body’s defenses 


* Some infections do not cause disease 

portals of entry

* skin
* mucous membrane
* **MAIN PORTAL OF ENTRY**
* placenta parenteral route

skin portal of entry

* Stratum corneum helps prevent many infections, but only as long as it remains intact 


* Other pathogens can enter through natural openings: hair follicles, sweat glands 
* Anything that opens the skin can lead to infection 


* Sweat glands, oil glands

mucous membrane portal of entry

* **MAIN PORTAL OF ENTRY** 


* The epithelial lined body cavities that are open to the environment 
* This is the major portal for most microbe entry 
* GI tract, Respiratory, Urinary, Reproductive and the conjunctiva 
* The most common portal is the respiratory system 
* List some pathogens that enter via the respiratory route below

placenta portal of entry

* Only a few types of pathogens can directly cross the placenta 
* In the small percentage that do, there can be severe consequences to the embryo, fetus, or mom 
*  E.g. – If measles is able to cross the placenta it can cause fatal encephalitis in the fetus 

parenteral portal of entry

* This is not a traditional route of entry, but a way in which pathogens are deposited directly into tissues 
* needle sticks, thorns or stepping on rusty nails 


* Cut in the skin 

adhesion factors

* Viruses and bacteria most commonly use lipoprotein or glycoprotein ligands that allow them to \n attach to receptors on the host cells
* The specific interaction of adhesions to their host cells often determines which types of hosts they \n can infect
* Some pathogens only have one type, others can have multiple
* Some are able to change their adhesions over time to evade the host’s immune system
* If a virus or bacteria loses the ability to make a specific adhesion protein it will become avirulent

biofilm facilitating contamination and infection

* many organisms only cause disease when they are in biofilm form 
* Some bacteria will change their phenotype drastically when in a biofilm 

infection

When a pathogen invades a host

disease

When the injury caused by the pathogen is significant enough to interfere with normal functioning of the host

morbidity

the condition of suffering from a disease or medical condition

pathogenicity

the ability to cause disease

virulence

the degree of pathogenicity and is enhanced by virulence factors

symptoms

* More subjective 
* Pain 
* Nausea 
* Headache 
* Sore throat 


* Fatigue 
* Itching, cramps etc. 

signs

* Objective signs of disease that are measurable 
* Swelling 


* Rash or redness 
* Vomiting 
* Diarrhea 
* Fever 
* Recommended treatment is above 100.5 


* Increase or decrease in WBC’s 
* Increase or decrease in HR 
* Increase or decrease in BP 

syndromes

* A group of signs and symptoms that characterize a disease 


* AIDS – hallmarks are malaise, decrease in T4 cells, diarrhea, weight loss, pneumonia, other rare 
* Fungal infections and cancers 

asymptomatic

* Lack observable signs or symptoms  
* May still be detected by proper testing 


* Some types of herpes virus infections are asymptomatic 
* Person may be able to transmit disease to others 

etiology

The cause for a disease 

* Some conditions are named for the disease and not the specific pathogen

koch’s postulates

* the gold standard for determining infectious disease 


* The suspected agent must be present in every case of the disease 
* The agent is isolated and grown in pure culture 
* The cultured agent must cause disease when inoculated into healthy host 


* The same agent should be found in the diseased host 
* Must be followed in order. – E.g., Haemophilus influenzae

koch’s postulates limitations

* Some pathogens cannot be grown in lab 
* Some diseases are caused by a combination of pathogens 
* Some are polymicrobial 
* Combination of pathogens working together 
* Like some are only infectious when they form biofilms 


* It is unethical to test human diseases using Koch’s postulates 
* Some diseases are named for what they affect rather than a specific pathogen

virulence factors

* extracellular enzymes
* endotoxins
* exotoxins
* things that block phagocytosis

extracellular enzymes + virulence

* Hyaluronidase – destroys hyaluronic acid, a key substance in ground substances of CT 
* Collagenase – destroys collagen allowing bacteria to spread. 
* Coagulase – causes blood clotting (coagulase test) 
* Staph aureus and strep are known to do this 
* Clots protect the bacteria 


* Kinases (Streptokinase, Staphylokinase) – digest blood clots and release bacteria 
* Allows them to spread through the body 

endotoxins + virulence

* Only produced by **gram negative cells** 
* The lipid A component of a gram-negative cell wall 
* Most common 
* Released when cells die 
* endCan cause fever, hemorrhage, inflammation 


* Released when the cells die or are destroyed by the host 
* Can cause – fever, inflammation, diarrhea, hemorrhage, shock, coagulation

exotoxins + virulence

* can be produced by gram negative and positive bacteria 


* produced and released by the bacteria 
* Cytotoxins 
* Kill cell membranes 
* Neurotoxins 
* Nervous tissue 
* Botulinum 
* Damages synaptic transmission (nerve to nerve and nerve to muscle) 
* Enterotoxins 
* GI tract 


* Our bodies can produce antibodies that will neutralize exotoxins before they make us sick 


* Vaccines that look for exotoxins are looking for a certain protein signature 

endotoxins vs exotoxins

Exotoxins are more serious than endotoxins, but if a large number of gram-negative cells die then endotoxins can cause disease 

* Need smaller number of exotoxins to cause disease 
* Onset of disease from exotoxin is more rapid and severe right off the bat 
* For endotoxins they take longer to cause disease 

infectious disease stages

1. incubation period
2. prodromal phase
3. illness period (climax)
4. decline
5. convalescence

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**You can be infectious at any stage** 

antiphagocytic factors + chemicals

* Capsules – are composed of the same things as body cells
* Can evade detection for longer
* Some capsules also make the bacteria very slippery and had to grab
* Antiphagocytic Chemicals – chemicals produced by bacteria that prevent lysosomes in the phagocytes from attaching to the bacteria and allows them to survive inside the phagocytes
* E.g. – M factor produced by Strep pyogenes

incubation period

the time between entry of the microbe and symptom appearance 

* Many infectious agents this is between 1-7 days 


* Depends on virulence of microorganism and infective dose 
* State and health of host (faster infection if immunocompromised) 
* Site of infection 

prodromal phase

a time of mild signs or symptoms 

* Mild signs and symptoms 


* Some infectious diseases that can skip the prodromal phase (GI bugs) 

illness phase

known as climax

* when signs and symptoms are most intense 
* Most severe part 
* When you feel the worst 
* The hosts immune system has not responded adequately yet or it is completely overwhelmed 


* Often but not always the most infective stage 

decline phase

As signs and symptoms subside 

* Immune system starts to recover or when antibiotics or antiviral meds kick in 
* When fever goes away but still sick 

convalescence phase

The body systems return

* Length depends upon same factors that cause disease (no co-morbidities) 

vehicle transmission

Airborne 

* When it is small enough to be picked up in air currents 


* Much more common occurrence with dental and surgical drills 

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Waterborne 

* Can act as a reservoir as well 
* Fecal-oral route 

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Foodborne 

* Another fecal-oral route 
* From improper food handling 

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Bodily fluids 

* Considered underneath water transmission 


* Can be a form of direct contact 
* Blood or semen come in contact with open cut 
* Should always be treated as if they contain pathogens 

vector

Biological 

* Bites 
* Insects 
* Mosquito is most common 

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Mechanical 

* Indirect transmission 


* e.g., fly walks on sandwich 

contact transmission

Direct 

* Bodily contact 


* Touching, kissing, sex,  
* Biting or scratching in zoonoses 
* Vertical transmission 


* Mom passes it to the baby via placentas 

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Indirect 

* Fomites – inanimate objects that are capable of transferring pathogens 


* e.g., toothbrush, medical equipment, money 

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Droplet 

* Droplets of mucous propelled out of nose or throat when talking, sneezing, coughing 
* Most travel 1m or less 

droplet vs airborne transmission

* Distance 


* Aerosols/airborne remain suspended in the air 

classifications of infectious diseases

* By taxonomic group 
* By body system affected 
* Longevity and Severity

acute diseases

* Symptoms develop rapidly and runs its course quickly 
* e.g., influenza, rotavirus, strep throat 

chronic diseases

* Disease with usually mild symptoms that develop slowly and a long time 
* e.g., COPD (Chronic Obstructive Pulmonary Disease), cancer, mono 

subacute disease

* Disease whose time course and symptoms range between acute and chronic 
* e.g., COVID 

latent disease

* disease that appears a long time after infection
* e.g., Proin diseases, Cold sores 

local infection

* infection only in a specific area of the body
* e.g., Tick bite 

communicable disease

Able to be transmitted from one host to another

noncommunicable disease

disease not passed from person to person

contagious disease

communicable disease that is easily spread

epidemiology

* The study where, when, and how diseases occur 
* How diseases affect the population 
* Can be applied to chronic diseases not just acute

incidence rate

* number of new cases that are appearing in a specific time 


* Better for ongoing outbreak

prevalence rate

* the total number of cases appearing in a specific time 


* Better for the burden of disease 

endemic

* naturally occurring in a population/normally around 


* Common cold 

sporadic

* few cases of diseases that pop up 


* Can be related or unrelated 

epidemic

* large new emergence of disease in an area 


* More cases than normally predicted for a given region 
* Continued or sustained spread of disease 


* Different than outbreak 
* Outbreaks are limited 
* Not enough momentum or population to keep the outbreak going 
* Outbreak of food poisoning

pandemic

worldwide epidemic

epidemiological approaches

Descriptive 

* Early studies 


* Trying to figure out what the cause it 
* What the reservoirs are 
* Index case – person who is the original host or reservoir 

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Analytical 

* Used to try to find associations between risk factors and behavior patterns of disease 


* Often retrospective studies (after the fact) 

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Experimental  

* Highest level of epidemiological studies 
* Hypothesis generating and testing experimental studies based upon previous information 

healthcare associated diseases

Types of HAIs

* Exogenous – picked up in a healthcare setting
* Endogenous – opportunists because of treatment
* Iatrogenic – caused by things like catheters, surgery, wrong antibiotics

Handwashing protocols can reduce infection by more than 50%

factors affecting HAIs

* Presence of microbes in the hospital setting
* Immunocompromised patients
* Transmission of pathogens between staff, and patients

specific immune response

adaptive 

* Humoral – B-cell mediated 
* Cell based – T-cell mediated 

nonspecific immune response

innate 

* Mechanical 
* Cells  
* Chemicals 
* Inflammation 
* Major component of immune response 
* Does not know the difference between sprain or bacteria

mechanical barriers

keep pathogens out 

* Skin 
* Secretions 
* Oils on skin 
* Sweat 


* Tears 
* Saliva 
* Mucosa 

cells

complement

* Made of about 20 proteins that are activated when exposed to bacterial antigens 
* For generalized bacterial infections 
* Series of proteins found in our blood 


* Some are part of the hemoglobin molecule 

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Classical Pathway 

* Stimulation by antigen-antibody complex 

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Alternate Pathway 

* Stimulation by microorganism cell wall 


* Literally pokes a hole in the wall of pathogens 

interferon

* Part of non-specific immune response 
* Generalized viral infections 
* Infected cell (host 1) will die, but interferon will cause neighboring cells to produce protective anti-viral protein coats 
* IFN’s used to treat some forms of Herpes and Hepatitis 


* Also used for autoimmune disorders 
* MS  


* Cells can produce interferon 


* Moves to neighboring cells and telling it to protect themselves

toll like receptors

* Integral proteins found on the cell membrane of phagocytes
* Trigger your body’s responses to a number of various bacterial and viral pathogens
* There are 10 different TLR’s found on human phagocytes
* Binding of Pathogen Associated Molecular Patterns (PAMP) triggers infected cells to do things \n like: apoptosis, initiate the inflammatory mechanism, or stimulate the adaptive response

neutrophils

* phagocytes – about 126 billion/day produced
* Usually the first WBC to make it to an infection
* 1 time use (like a honeybee stinger)
* Pus =dead neutrophils, microbes, pathogens

macrophages

* monocytes in blood, macrophages in tissue
* Leave blood and increase numbers at site of infection
* They are the cleanup crew
* Include many different types – dendritic cells, microglia, alveolar, hepatic

basophils

* mobile
* Release factors which attract more WBC’s (chemotactic factors)

mast cells

* nonmobile
* Are found near sites of possible pathogen influx
* Release chemotaxic factors
* Can also phagocytose bacteria

eosinophils

Act as moderators of inflammatory response and kill parasites by releasing enzymes all over them